Research in virology at Columbia University has historically been at the forefront of this discipline. For more than a decade the four research groups of Stephen Goff, Vincent Racaniello, Saul Silverstein and Hamish Young have worked together at Columbia University to develop new technologies, uncover mechanisms of virus infections and pathogenesis and to develop genetic systems for their respective groups. Contributions from these of four laboratories have provided important tools for the development of virology. For example, Goff and his colleagues were the first to clone the MLV genome and apply the tools of molecular genetics to the analysis of the genes that compose this virus. His group was the first to clone and express reverse transcriptase. They were also the first group to knockout a gene in mice, the Abl gene, and study its function in development. Racaniello and his colleagues were the first to clone a complete infectious RNA animal genome from an RNA virus and they too have applied the tools of molecular genetics to the study of this genome. In 1989 he and his colleagues cloned the first enterovirus receptor and subsequently created a transgenic mouse for studying virus pathogenesis and assessing the utility of new vaccines. Silverstein and his colleagues were the first to demonstrate that shut off of host protein synthesis by herpes simplex virus (HSV) resulted from a virion component. In 1976 he and his colleagues were the first to isolate the thymidine kinase gene and use it to biochemically transform cells in culture. These studies formed the basis for the isolation of mammalian genes, the commercial production of pharmaceuticals such as EPO, TPA, Factor VIII and other important molecules as well as establishing the technology for the analysis of genes after transient transfection. In other studies they were among the pioneers in the use of this technology for the analysis of the regulatory properties of HSV genes. The Young laboratory was the first to study pools of recombining molecules in animal cells. They also furthered the development the overlap recombination for the construction of adenovirus vectors. These analyses provided important information regarding the homology requirements for successful recombination events in animal cells. Their recent forays into transcription control of the adenovirus major late promoter have unveiled new paradigms for regulation of this important control unit. Thus, as a group, these four investigators have made significant contributions to the discipline of virology. What is not as apparent from these advances is the contribution of each of these groups to the others' scientific programs.